Abstracts

Rationale: Mutations in dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) have been implicated in DYRK1A-related intellectual disability (ID) syndrome, which is characterized by intellectual disability, autism spectrum disorder, facial dysmorphisms and microcephaly. About half of affected individuals develop epilepsy with various seizure types. There are limited reports describing the epilepsy phenotype of patients with DYRK1A-related ID, and to our knowledge, there are no previous reports of patients with low CSF glucose or patients having a glucose-transporter-1 (GLUT1) deficiency-like phenotype. Methods: This report describes the epilepsy and clinical features of four children identified at our centre with de novo* DYRK1A variants and associated intellectual disability and epilepsy. Genetic abnormalities were found by either whole exome sequencing performed through 2 different studies or chromosome microarray. CSF analysis was performed in 2 patients. Results: All four patients were females and patients' ages ranged from 5 to 12 years at last examination (Table 1). Median age at seizure onset was 2 years (range 22-36 months). All patients had generalized tonic- clonic seizures, which were triggered by fever in 3 patients. GLUT1 deficiency was considered in patients #1 and #2 due to the presence of microcephaly, developmental delay and treatment resistant epilepsy (#1 with absence seizures starting Conclusions: This report expands the epilepsy phenotype of patients with DYRK1A-related ID syndrome. Two patients had overlapping features with GLUT1 deficiency including low CSF glucose and ratio, and one patient became seizure free on the ketogenic diet. This might have important treatment implications for patients with DYRK1A-related ID. Identification of additional patients with a similar phenotype is required to support our findings and further functional studies are planned to identify how DYRK1A mutations might impact CSF glucose levels. Funding: None specifically